Neurotransmitter Transporters As Targets For The Nerve Drug Screening

Dopamine transporter (DAT) is an important target, to which a lot of medicines and drugs directly bind to regulate the function of dopaminenergic neural system. We found a compound isolated and purified from a natural medicine, which specially enhanced the dopamine reuptake by DAT. We called it SZ92. At the concentration of 0.1μM of dopamine, the value of EC50 of SZ92 is 1.44μM; and the most effective concentration of SZ92 is 10μM, at which the dopamine reuptake is increased by 298.1%. The results of dynamic experiments did not indicate that SZ92 altered the value of Km or Vmax of reuptake response. It reversed the inhibition on DAT by cocaine, but did not compete for the same binding sites on DAT with cocaine. Neither did it enhance DA reuptake by improving the expression of DAT on presynaptic membrane. Its activation was not influenced by concentration gradient of Ca²⁺, Mg²⁺ or ATP. Structure-activation relationship implied the number and sites of substituent making good sense to SZ92. The results of our research imply that SZ92 is a potent DAT activator, as well as a potential medicine used for diseases of dopaminenergic system.